Phase I study of oxaliplatin in patients with advanced cancer.
Oxaliplatin, or trans-1-diaminocyclohexane-platinum, was tested in a phase I study. A total of 44 patients received 116 courses with dose escalation from 45 to 200 mg/m2. Neither renal nor hematologic toxicities were observed at doses up to 200 mg/m2. Gastrointestinal toxicity was practically constant and often of grade 3-4 on the WHO scale (53% of patients). The dose-limiting toxicity was a peculiar sensory neuropathy; the first neurologic phenomena appeared at a dose of 135 mg/m2 and continued thereafter, occurring after 75% of the courses with mild to moderate intensity (WHO grade 1-2 after 67% of the courses). Neurotoxicity was cumulative and six patients developed grade 3 disabling neuropathy after a cumulative dose of 500 mg/m2, with walking and handwriting difficulties being slowly regressive in three cases. A peculiar symptom was the influence of temperature, with exacerbation of parethesias when patients touched cold surfaces. Nerve-conduction studies carried out in six cases showed a predominantly sensory neuropathy with axonal degeneration. No other toxicities were observed, although audiograms were not systematically done. We observed four partial responses that lasted 6-13 months in patients with oesophageal (2 cases), lung (1), and urothelial cancer (1); two of these patients had been pretreated with cisplatin. Since neurologic side effects occur very frequently and may produce a long-lasting sensory neuropathy, for phase II studies we recommend a starting dose of 135 mg/m2, with a careful neurologic survey.
Extra
J M
JM
Service d'Oncologie Médicale, l'Hôpital Saint Louis, Paris, France.
Espie
M
M
Calvo
F
F
Ferme
C
C
Mignot
L
L
Marty
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009422:Nervous System Diseases / Q000139:chemically induced; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010292:Paresthesia / Q000139:chemically induced; D014839:Vomiting / Q000139:chemically induced
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin